Hypertension is a multifactorial disease that affects 25% of all adults in the United States. Environmental and genetic factors are both important in the pathogenesis of hypertension. Folate has important beneficial effects on endothelial function, and endothelial dysfunction may be pathogenic in hypertension. The impact of folate on endothelial function may be mediated by nitric oxide, homocysteine, or both. In addition, certain polymorphisms in endothelial nitric oxide synthase (eNOS) and methylenetetrahydrofolate reductase (MTHFR) genes may be associated with endothelial dysfunction and hypertension. Taken together, a high dietary folic acid intake may reduce the risk of incident hypertension, and may modify impact of eNOS and MTHFR polymorphisms on the risk of hypertension. Using two large independent cohorts, the risk of incident hypertension will be prospectively analyzed according to folic acid intake (>80,000 total subjects, >18,000 cases of hypertension). Subsequently, the risk of hypertension will be analyzed in > 2000 men and women genotyped for eNOS, and > 7000 men and women genotyped for MTHFR. Interaction with folate will be analyzed. [unreadable] [unreadable]